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Objectives: Microcrystal-induced arthritis is still an unresolved paradigm for medicine. Overt inflammation may be absent even when crystals occur in SF. Recently, the production of neutrophil extracellular traps (NETs) embedding MSU crystals has been proposed as a possible mechanism of the auto-resolution of the inflammatory phase during gout. We aimed to verify and quantify the release of NETs in SFs during gout and pseudogout attacks and to compare any differences with respect to crystals and neutrophils number, and to analyse activation of necroptosis pathway in SF from crystal-induced arthritis., Methods: SF samples were obtained by arthrocentesis from 22 patients presenting acute crystal-induced arthritis, gout or pseudogout (n = 11 each group), and from 10 patients with acute non-crystal arthritis as controls. NETosis was quantified in SF by nucleic acid stain and by quantification of human neutrophil elastase. Activation of phosphorylated MLKL was assessed by western blot., Results: We observed that SF neutrophils encountering MSU and CPPD crystals during episodes of gout and pseudogout release NETs in relation to the number of crystals in SF and irrespective of neutrophil density and type of crystal. This release was accompanied by necroptosis through the activation of the MLKL pathway., Conclusions: Our findings suggest that a role of NETs in crystal-induced arthritis is to 'trap extracellular particles', including microcrystals. Embedding crystals in aggregates of NETs may be the basis of tophi and CPPD deposition, and may have implications for disease evolution rather than for spontaneous resolution of the acute attack., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Calcium pyrophosphate crystal deposition disease (CPPD) is a common cause of acute and chronic arthritis, especially in the elderly population. There is a paucity of data regarding the management of CPPD disease, which is currently based on expert opinion and evidence derived from the treatment of gout. We conducted a systematic literature review in order to identify the available treatment options for CPPD, and describe their efficacy and safety., Material and Methods: Online databases were searched from inception to May of 2020 using the search terms: (CPPD [Title/Abstract] OR CPDD [Title/Abstract] OR calcium pyrophosphate [Title/Abstract] OR chondrocalcinosis [Title/Abstract]) AND (treatment [Title/Abstract] OR management [Title/Abstract] OR therapy [Title/Abstract]). Articles evaluating the use of specific treatment agents for CPPD were eligible for inclusion. Case reports were excluded., Results: A total of 22 eligible studies and 403 unique patients were selected. We identified only 3 randomized, double-blind, controlled trials (RCTs) evaluating the use of methotrexate, hydroxychloroquine, and magnesium carbonate in CPPD, and these therapeutic options, with the exception of methotrexate, have shown efficacy and reduction of pain intensity. Further, 10 case series and 9 cohort studies were included. Intramuscular and intra-articular glucocorticoids, ACTH, as well as the biologic agents anakinra and tocilizumab appear to be efficacious in CPPD. Intra-articular injections of glycosaminoglycan polysulphate, hyaluronic acid and yttrium, as well as synovial membrane destruction by laser irradiation were associated with symptomatic improvement. Due to significant study heterogenicity, direct comparison between studies was not possible., Conclusion: There are a limited number of studies evaluating the treatment of CPPD. High quality evidence is rather limited, while commonly administered agents such as NSAIDs, colchicine and corticosteroids have not been evaluated by RCTs. The need for high quality evidence supporting specific treatment modalities is urgent for this common yet neglected form of arthritis., Competing Interests: Declaration of Competing Interest All authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: A hot, swollen joint is a common clinical condition encountered in the ED and elective orthopaedic and rheumatology clinics. These patients can be difficult to manage and properly treat., Aims and Objectives: The aim of this study was to report a single centre retrospective analysis of patients presenting to our institution for a hot, swollen joint over a three-month period., Methods: The study included patients presenting with a hot, swollen joint to ED or electively to clinics. The synovial fluid was aspirated and sent for microbiological and cytological investigation. P value was set to < 0.001. 36 patients (22 M, 14 F) with a mean age of 72.8 ± 17.4 years met our criteria. 20 cases (55.6 %) involved the knee joint, the wrist in 10 cases (27.8%), the elbow in 3 cases (8.3%) and the shoulder in 3 cases (8.3%)., Results: Of the 36 synovial fluid samples collected, only 7 (19.4%) reported evidence of infection. On cytological examination of the synovial fluid, 21 (58.3%) reported presence of calcium pyrophosphates crystals (Pseudogout), 4 (11.1 %) reported presence of uric acid crystals (Gout) and 11 (30.5%) reported absence of crystals. We found a significant correlation between age and the diagnosis of pseudogout and between previous antibiotic treatment and ED presentation. Our study sheds light on the high incidence of crystal-related pathologies., Conclusion: In order to improve our management of this common condition and enhance our understanding of the clinical diagnosis in certain patient population, further high-profile clinical studies are needed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: In this retrospective observational study, we assess the efficacy and safety of the interleukin 1 receptor antagonist anakinra in medically complex, hospitalized patients with acute gout and calcium pyrophosphate crystal arthritis., Methods: Adult inpatients treated with anakinra from 2014 to 2017 were identified for inclusion. Charts were reviewed for demographics, comorbidities, laboratory data, pain scores, joint involvement, prior treatment, dosing and response to anakinra, concurrent infections, and surgical interventions. Response to anakinra treatment was determined from review of provider documentation, as well as recorded pain scores on a numeric scale., Results: We identified 100 individuals accounting for 115 episodes of arthritis. This population was 82% male, with an average age of 60 years. Comorbidities included renal disease (45%) and history of organ transplantation (14%). Twenty-nine episodes of arthritis occurred in the perioperative setting. Concurrent infection was present in 34 episodes. Eighty-six episodes of arthritis had partial or complete response to anakinra within 4 days of treatment initiation; 66 episodes had partial or complete response within 1 day of anakinra administration. Anakinra was well tolerated., Conclusion: To our knowledge, this is the largest observational study of anakinra use in the inpatient setting for the acute treatment of crystal-associated arthritis. We observed a rapid response to anakinra, with 75% of episodes significantly improving or completely resolving within 4 days of the first dose. Our data also support the use of this biologic agent in individuals with infections, as well as perioperative individuals and immunosuppressed transplant recipients.

Calcium pyrophosphate dihydrate (CPPD) deposition disease is a metabolic arthropathy which results from deposition of calcium pyrophosphate crystals in and around joints especially the hyaline cartilage and disc material. This metabolic disease in uncommon in the smaller joints and multiple diagnostic modalities along with biochemical investigations would be necessary for definite diagnosis. We highlight the case of a 48 year old male who presented with a painful mass at the base of left thumb and was clinic-radiologically suspected as malignancy. Cytological examination (fine needle aspiration cytology [FNAC]) showed numerous extracellular rods shaped and rhomboid blunt-ended crystals along with foreign body type of giant cells. The main emphasis here is on the pivotal role played by FNAC in accurately diagnosing the disease where other modalities like radiology and histopathology failed to do so. The exact categorization of crystals is important from treatment point of view to avoid any major deformities in the joints/systemic manifestation., (© 2018 Wiley Periodicals, Inc.)

Background: ACTH, a member of the melanocortin group of proteins, has long been used in the treatment of gout and is considered as an alternative therapeutic option, especially in difficult-to-treat patients., Methods: We performed a systematic electronic search (Medline and ScienceDirect) using the keywords gout, treatment, ACTH, adrenocorticotropic hormone, and pseudogout. We identified 5 studies assessing the efficacy of ACTH in acute crystal-induced arthritis., Results: In the studies for acute gout, a total of 266 patients have been treated with ACTH; treatment was highly efficacious with a response rate of 77.9-100%. Only few side effects, such as hyperglycemia, hypokalemia, and edema, were reported, all of which were mild. The available evidence for acute CPP crystal arthritis is limited. A total of 19 patients have been assessed in retrospective studies; the response rate was 90-100%, whereas no significant side effects were recorded. The mechanism of action of ACTH in acute crystal-induced arthritis is not entirely known but seems to extend beyond stimulation of steroid release from the adrenal glands; ACTH is able to stimulate melanocortin receptors on macrophages and downregulate gouty inflammation., Conclusions: Data suggests that ACTH is effective in acute crystal-induced arthritis and may be a first-line therapy in patients with multiple medical problems. We propose that further evaluation of ACTH should be performed, with a large-scale, randomized controlled study focusing on safety issues in patients with multiple comorbidities., (© 2013 Published by Elsevier Inc.)

Calcium pyrophosphate deposition (CPPD) is a condition where calcium pyrophosphate crystals cause arthritis. Its occurrence in the temporomandibular joint (TMJ) is sparingly reported in the literature. Non-surgical treatment modalities consist of non-steroidal anti-inflammatory drugs, colchicine, and intra-articular cortisone injection. In the TMJ, previous reports have described resection of affected joint with reconstruction. We present a case of an extensive CPPD lesion affecting the left TMJ requiring surgical resection and reconstruction with a custom made TMJ prosthesis alongside with a review of the existing literature.

Introduction: This study aimed to compare the efficacy of non‐loading versus loading low‐dose colchicine in patients with acute crystal‐associated arthritis. Materials and Methods: All in‐patients who were admitted to Chiang Mai University Hospital with non‐arthritis disease and developed acute crystal‐associated arthritis during admission (within 48 h after arthritis onset) were invited to join this study. The patients were randomized into two groups. Patients in Group I (non‐loading group) and Group II (loading group) received colchicine at 1.2 and 2.4 mg in the first 24 h, respectively. The primary outcome was the patients' pain response at 24 h after treatment. Results: Of 80 patients, 49 were acute gouty arthritis, and 31 acute calcium pyrophosphate (CPP) arthritis. The mean [95% CI] pain score was no different between Groups I and II at the baseline level (6.46[5.72–7.19] vs. 6.654[5.85–7.44], p =.867) and at 24 h (3.13[2.43–3.82] vs. 3.18[2.42–3.93], p =.907). The proportion of patients with ≥50% pain reduction was not different (57.50% vs. 55.00%, p =.822). Sensitivity analysis among patients with a baseline pain score of ≥4 showed the same pattern of response. Mild diarrhea was common and comparable in both groups. Subgroup analysis according to renal function (eGFR < 60 vs. ≥60 mL/min/1.73 m2) or type of crystals (acute gouty arthritis vs. acute CPP arthritis) also showed the same pattern of response. Conclusion: Non‐loading low‐dose colchicine was as effective as loading low‐dose colchicine in patients with acute crystal‐associated arthritis, regardless of renal function or type of crystals. [ABSTRACT FROM AUTHOR]

Crystalline arthropathies are well-known pathologies in a native knee; however, the literature is scarce with regards to crystalline arthropathies in a total knee arthroplasty (TKA). The presentation of crystalline arthropathy in a TKA can be similar to a periprosthetic joint infection (PJI), making it difficult to distinguish between the 2 diagnoses. We present 1 case highlighting the similarity between crystalline arthropathy and PJI. A 71-year-old man with a history of bilateral TKAs presented with bilateral painful knee effusions and was initially presumed to have PJIs; however, he was later diagnosed with gout and successfully treated medically. A complete review of the literature demonstrates that crystalline arthropathies after TKA are infrequently reported and can be difficult to decipher from PJIs, and there is a lack of standardized treatment.

The development of microcrystalline arthritides is most frequently associated with the formation of monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals. Their identification is of crucial importance in recognizing these diseases. Objective: to determine the possibilities of histological techniques in identifying MSU and CPP crystals and to evaluate the effectiveness of the techniques. Subjects and methods. Twenty-four tissue blocks (fragments of the affected areas of the elbow joint, the interphalangeal joint of the index finger, and hip joint) from 7 patients were examined. Paraffin sections were stained with a 0.5% alcohol solution of eosin, as well as with hematoxylin and eosin. Tissue specimens were examined and digitized using an AxioScope.A1 stereo microscope with Zenblue software (Carl Zeiss MicroImaging GmbH, Germany). Results and discussion. When staining the tissue sections with hematoxylin and eosin, microcrystals were not visualized; the major portions of MSU crystals was dissolved during fixation and staining, whereas CPP crystals were masked with hematoxylin as focal basophilic aggregates. The staining technique with an alcohol solution of eosin and short formalin fixation (within 12 hours) made it possible to avoid dissolution of MSU crystals and to visualize both MSU and CPP crystals, and to determine their shape and color. Conclusion. Light microscopy of the tissue sections stained with an alcohol solution of eosin along with short formalin fixation is a reliable method to differentiate MSU and CPP crystals. In patients undergoing endoprosthetic replacement, the significance of this technique for the pathomorphological study of surgical material consists in assessing inflammatory activity and in eliminating a disease, such as microcrystalline arthropathy.

Introduction: Crystalline arthritis (CA), characterized by acute joint pain and erythema secondary to calcium pyrophosphate deposition (CPPD, or pseudogout) or monosodium urate crystals (gout), is a potentially underreported complication following allogeneic hematopoietic cell transplant (alloHCT). Graft-versus-host disease prophylaxis with calcineurin inhibitors (CNIs) causes hypomagnesemia and hyperuricemia, resulting in CA. CA related to tacrolimus has yet to be characterized following alloHCT. Case report: We retrospectively reviewed records of 450 consecutive patients undergoing alloHCT and identified 15 (3.3% incidence) who developed CA on tacrolimus. Large joints were involved in 10 (66.7%) patients, all patients had recent hypomagnesemia, and no patient had hyperuricemia, suggesting CPPD was the most likely etiology. Management and outcome: Eleven (73.3%) patients received systemic corticosteroids; 6 as initial therapy and 5 added to or substituted for colchicine in the setting of slow or inadequate response. The median duration of corticosteroid therapy was 6 days, however 2 patients (13.3%) required prolonged maintenance due to recurrence. Eleven (73.3%) patients received colchicine; 9 as initial therapy and 2 added to or substituted for corticosteroids in the setting of slow or inadequate response. The median duration of colchicine therapy was 18 days. The median time to symptom resolution was 21 days. Discussion: Patients on tacrolimus following alloHCT presenting with acute joint pain and erythema should be evaluated for CPPD. Hypomagnesemia secondary to CNIs is likely the precipitating factor for CPPD in this population. Patients can effectively be managed with systemic corticosteroids and/or colchicine, however prolonged duration of treatment and even maintenance may be necessary. Based on the Naranjo Algorithm, CPPD secondary to tacrolimus induced hypomagnesemia is a possible adverse drug event, with a score of 3–4. [ABSTRACT FROM AUTHOR]

Pseudogout and gout are common types of inflammatory joint disease in the elderly. However, the existence of both in a single joint in a patient is relatively rare. This case report describes an interesting case of a 42-year old man who presented with simultaneous gout and pseudogout in the knee joint, diagnosed via polarised light microscopy. There was no radiographic evidence of pseudogout. This case report serves to illustrate the need to actively exclude concomitant pseudogout, especially in patients suffering from recurrent attacks of gout.

• The WBC count is useful for screening for the absence of crystals in synovial fluid. • Total protein concentration cannot discriminate between samples with and without crystals. • A WBC count lower than 1650/mm3 predict the absence of crystals with high sensitivity. Synovial fluid analysis is essential for diagnosing crystal-induced arthritis. Monosodium urate monohydrate (MSU) crystals in gout and calcium pyrophosphate dihydrate (CPP) crystals in pseudogout trigger inflammatory reactions that result in white blood cell (WBC) activation. This study aimed to evaluate the predictive value of synovial fluid WBC count and total protein concentration for the absence of microcrystals. This prospective study analyzed all synovial fluid samples collected at a single center in a 6–month period. The absolute WBC count and total protein concentration were recorded for each sample. A single expert used polarized light microscopy to detect microcrystals. Mann-Whitney U-tests was used to compare mean counts and concentrations in samples with and without crystals. Diagnostic performance was assessed through the area under the receiver-operating characteristic curve (AUC). A total of 205 samples were included. The absolute WBC count was significantly higher in samples with crystals than in those without. No differences were found between MSU and CPP. The ROC curve showed an AUC 0.773, and an absolute WBC count <1650/mm3 yielded 95.7% sensitivity, 53.1% specificity, and 97.7% negative predictive value for predicting the absence of microcrystals. Total protein concentration was not significantly different between samples with and without crystals. The WBC count is useful for screening for the absence of microcrystals in synovial fluid; the cutoff <1650 WBC/mm3 accurately predicts the absence of crystals, obviating the need for polarized light microscopy and thus simplifying and shortening laboratory analysis of synovial fluid, leading to a reduction in laboratory turnaround time. [ABSTRACT FROM AUTHOR]

Adverse reaction to metal debris (ARMD) is a known cause of failed metal in hip arthroplasty. Diagnosis of this type of prosthesis failure may be difficult, and the hallmark is an abnormally elevated serum cobalt level. Concomitant diagnoses may also be present, such as infection, instability, and loosening, and this may confuse interpretation of abnormal laboratories. We present here, for the first time, 2 patients with ARMD and crystalline arthropathy. In each case, the patient chose surgery for ARMD, with resolution of symptoms and no recurrence of the crystalline arthropathy. We present these cases to alert the orthopaedist that crystalline arthropathy may be present at the same time as ARMD, but is likely not the primary cause of symptoms.

Acute monoarthritis affects a single joint and has many potential underlying causes, including crystal deposition diseases, infection, trauma, and osteoarthritis. A comprehensive health history and physical examination can help narrow the list of differential diagnoses; judicious diagnostic testing can help pinpoint the diagnosis. Clinicians also must be able to recognize which patients require emergency referral to prevent long-term adverse consequences. [ABSTRACT FROM AUTHOR]

Abstract: Background: Literature pertaining to the predictive factors for septic arthritis is limited. Aims: The primary objective was to investigate the predictive factors for septic arthritis. The secondary objectives were to investigate the predictive factors for crystal arthritis and to explore current practices in the management of acute arthritis. Methods: A retrospective analysis was undertaken. All patients with an acute arthritis who underwent a joint aspiration for diagnostic and management purposes were considered for inclusion. The outcome measures were patient demographics, findings on physical examination, findings on blood and synovial fluid analysis and management. Results: Of the patients who presented with an acute arthritis, 24 of the 172 joint aspirations undertaken were positive for bacteria (13.95%). Of the 172 joint aspirations, 90 were positive for crystals (52.33%). Investigated variables associated with increased risk for the presence of bacteria on synovial fluid included features of sepsis (P < 0.001), joint‐restricted range of motion (P = 0.048), elevated C‐reactive protein (P < 0.001) and elevated total leukocyte count on synovial fluid (P < 0.001). Of the 24 joint aspirations that were positive for bacteria, 13 had associated positive blood cultures (54.17%). Of the 172 joint aspirations, antibiotics were administered in 96 cases (55.81%). Of these, antibiotics were administered prior to joint aspiration in 41 cases (42.71%). Conclusions: In our study, the most common cause of acute arthritis was crystal arthropathy. An accurate physical examination in conjunction with synovial fluid analysis is of particular importance in diagnosing septic arthritis. Blood cultures are not a reliable substitute for joint aspiration but should nevertheless be undertaken. [ABSTRACT FROM AUTHOR]

The anti-inflammatory and immunomodulatory effects of nanoparticles in several chronic diseases have been extensively researched. The aim of this review is to examine how nanoparticles modulate the inflammatory pathways that characterize the most prevalent forms of microcrystal-induced arthritis, including gout, pseudogout, and BCP-induced arthritis. The nanoparticles of chitosan-coated calcium phosphate, uricase, aceclofenac, and gold have been investigated in crystal-inducedarthritis. The most important results of the studies outlined in this review show that nanoparticles can inhibit the expression and the release of some pro-inflammatory mediators and proteolytic enzymes, and the activity of different transcriptional factors in vitro, as well as decrease the uric acid levels in several studies of in vitro and in vivo models of gout, which show interesting results in terms of decreasing the amount of crystals and tissue damage, respectively. In view of their multiple beneficial effects, nanoparticles can be considered a valuable therapy that contributes to the pharmacological treatment in crystalinduced arthritis. [ABSTRACT FROM AUTHOR]

Monoarthritis can be inflammatory or non-inflammatory, and can be acute or chronic. A thorough history and physical examination can differentiate inflammatory from non-inflammatory monoarthritis. The most common causes of acute inflammatory monoarthritis are infectious arthritis, crystal induced arthritis (gout and pseudogout). Examination of synovial fluid often is essential in making a definitive diagnosis. Immunoinflammatory diseases like rheumatoid arthritis, systemic lupus erythematosus, spondyloarthritis, Behηet′s disease, and reactive arthritis can all begin as acute inflammatory monarthritis. Synovial biopsy is useful to diagnose chronic infections like tuberculosis and brucellosis. In order to arrive at a final diagnosis other organ systems should be thoroughly reviewed, because other systemic illness like sickle cell disease, thalassemia, sarcoidosis can all cause monoarthritis.

Objective: To evaluate the efficacy and safety of anakinra in inpatient management of acute gout and pseudogout.Methods: Hospitalized patients with acute gout (n = 77) or pseudogout (n = 11) or both (n = 3) were analyzed for response to anakinra and adverse effects.Results: Half of all patients had comorbidities limiting the treatment choice. Anakinra was well tolerated, and 92% of gout flares and 79% of pseudogout flares responded to treatment.Conclusion: Anakinra is an effective and safe treatment for acute gout and pseudogout in hospitalized patients, particularly in those with comorbidities. [ABSTRACT FROM AUTHOR]

We review entities that have historically been thought to be pseudotumors or mimics of bone tumours. We discuss tumifactive amyloid deposits, the brown tumours of hyperparathyroidism, the various types of cysts that can be seen in bone, Nora lesion, subungual exostosis, haemophilic pseudotumors, non-ossifying fibroma, fibrous dysplasia, osteofibrous dysplasia, Paget disease, tophaceous gout and pseudogout. [ABSTRACT FROM AUTHOR]